Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative diseases mainly composed of typical autosomal recessive lysosomal storage disorders. The NCLs can be characterized by clinical manifestations like progressive mental deterioration, cognitive impairment, visual failures, seizures and deteriorating motor function accompanied by histological findings such as the accumulation of autofluorescent storage material in neurons or other cell types (1). The NCLs have been subdivided into several groups (Type1-10) based on the age of onset, ultrastructural variations in accumulated storage materials, and genetic alterations unique to each specific disease type (2, 3).
Late infantile neuronal ceroid lipofuscinosis (Jansky-Bielschowsky disease, LINCL, Type 2) typically produces symptoms at the age of 2-4 years, progresses rapidly and ends in death between ages 8 to 15 as a result of a dramatic decrease in the number of neurons and other cells (2, 4). LINCL is associated with mutations in the Cln2 gene, a 13 exon and 12 intron gene of total length of 6.65 kb mapped to chromosome 11p15.5. The Cln2 gene encodes lysosomal tripeptidyl tripeptidase I (TPP-I or pepstin insensitive protease), a 46 KD protein that function in the acidic environment of the lysosomal compartment to remove tripeptides from the amino terminus of proteins (5, 6). This mutation in the Cln2 gene results in a deficiency and/or loss of function of the TPP1 protein that leads to intralysosomal accumulation of autofluoroscent lipopigments known as ceroid-lipofuscin (5). Currently there is no established treatment or drugs available for this disease; all approaches are merely supportive or symptomatic, indicating a need for novel therapeutic approaches (7). However, there are different variants of Cln2 mutations and there have been reports that residual TPP-I activity can be found in patients with LINCL, indicating that there must be a few copies of normal Cln2 gene remaining in patients affected with LINCL (8, 9).